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Summary: Awareness of the prevalence of osteoporosis and fractures across jurisdictions can guide the development of local preventive programs and healthcare policies. We observed geographical variations in total hip bone mineral density and in the prevalence of major osteoporotic fractures across Canadian provinces, which persisted after adjusting for important covariates. Purpose: We aimed to describe sex-specific total hip bone mineral density (aBMD) and prevalent major osteoporotic fractures (MOF) variation between Canadian provinces. Methods: We used baseline data from 21,227 Canadians (10,716 women, 10,511 men) aged 50–85 years in the Canadian Longitudinal Study on Aging (CLSA; baseline: 2012–2015). Linear and logistic regression models were used to examine associations between province of residence and total hip aBMD and self-reported MOF, stratified by sex. CLSA sampling weights were used to generate the prevalence and regression estimates. Results: The mean (SD) age of participants was 63.9 (9.1) years. The mean body mass index (kg/m2) was lowest in British Columbia (27.4 [5.0]) and highest in Newfoundland and Labrador (28.8 [5.3]). Women and men from British Columbia had the lowest mean total hip aBMD and the lowest prevalence of MOF. Alberta had the highest proportion of participants reporting recent falls (12.0%), and Manitoba (8.4%) the fewest (p-value=0.002). Linear regression analyses demonstrated significant differences in total hip aBMD: women and men from British Columbia and Alberta, and women from Manitoba and Nova Scotia had lower adjusted total hip aBMD than Ontario (p-values<0.02). Adjusted odds ratios (95% confidence intervals, CI) for prevalent MOF were significantly lower in women from British Columbia (0.47 [95% CI: 0.32; 0.69]) and Quebec (0.68 [95% CI: 0.48; 0.97]) and in men from British Columbia (0.40 [95% CI:0.22; 0.71]) compared to Ontario (p-values<0.03). Results were similar when adjusting for physical performance measures and when restricting the analyses to participants who reported White race/ethnicity. Conclusion: Geographical variations in total hip aBMD and in the prevalence of MOF between provinces persisted after adjusting for important covariates which suggests an association with unmeasured individual and environmental factors. [ABSTRACT FROM AUTHOR]

Summary: Prior non-vertebral fractures, except of the ankle, are associated with increased likelihood of vertebral fracture. As knowledge of vertebral fracture presence may alter care, vertebral fracture assessment (VFA) is indicated in patients with prior fracture. Introduction: Vertebral fractures are often unappreciated. It was recently advocated that all Fracture Liaison Service (FLS) patients have densitometric VFA performed. We evaluated the likelihood of vertebral fracture identification with VFA in patients with prior fracture using the Manitoba Bone Density database. Methods : VFA was performed in patients with T-scores below − 1.5 and age 70 + (or younger with height loss or glucocorticoid use) obtaining bone densitometry in Manitoba from 2010 to 2018. Those with prior clinical vertebral fracture, pathologic fracture, or uninterpretable VFA were excluded. Vertebral fractures were identified using the modified ABQ method. Health records were assessed for non-vertebral fracture (excluding head, neck, hand, foot) diagnosis codes unassociated with trauma prior to DXA. Multivariable odds ratios (ORs) for vertebral fracture were estimated without and with adjustment for age, sex, body mass index, ethnicity, area of residence, income level, comorbidity score, diabetes mellitus, falls in the last year, glucocorticoid use, and lowest BMD T-score. Results: The study cohort consisted of 12,756 patients (94.4% women) with mean (SD) age 75.9 (6.8) years. Vertebral fractures were identified in 1925 (15.1%) overall. Vertebral fractures were significantly more likely (descending order) in those with prior pelvis, hip, humerus, other sites, and forearm, but not ankle fracture. There was modest attenuation with covariate adjustment but statistical significance was maintained. Conclusions: Prior hip, humerus, pelvis, forearm, and other fractures are associated with an increased likelihood of previously undiagnosed vertebral fracture, information useful for risk stratification and monitoring. These data support recommending VFA in FLS patients who are age 70 + with low BMD. [ABSTRACT FROM AUTHOR]

Summary: The G arvan Fracture Risk Calculator predicts risk of osteoporotic fractures. We evaluated its predictive performance in 16,682 women and 2839 men from Manitoba, Canada, and found significant risk stratification, with a strong gradient across scores. The tool outperformed clinical risk factors and bone mineral density for fracture risk stratification. Introduction: The optimal model for fracture risk estimation to guide treatment decision-making remains controversial. Our objective was to evaluate the predictive performance of the Garvan Fracture Risk Calculator (FRC) in a large clinical registry from Manitoba, Canada. Methods: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women and men aged 50–95 years undergoing baseline BMD assessment from September 1, 2012, onwards. Five-year Garvan FRC predictions were generated from clinical risk factors (CRFs) with and without femoral neck BMD. We identified incident non-traumatic osteoporotic fractures (OFs) and hip fractures (HFs) from population-based healthcare data sources to March 31, 2018. Fracture risk was assessed from area under the receiver operating characteristic curve (AUROC). Cox regression analysis and calibration ratios (5-year observed/predicted) were assessed for risk quintiles. All analyses were sex stratified. Results: We included 16,682 women (mean age 66.6 + / − SD 8.7 years) and 2839 men (mean age 68.7 + / − SD 10.2 years). During a mean observation time of 2.6 years, incident OFs were identified in 681 women and 140 men and HFs in 199 women and 22 men. AUROC showed significant fracture risk stratification with the Garvan FRC. Tool predictions without BMD were better than from age or decreasing weight, and the tool with BMD performed better than BMD alone. Garvan FRC with BMD performed better than without BMD, especially for HF prediction (AUROC 0.86 in women, 0.82 in men). There was a strong gradient of increasing risk across Garvan FRC quintiles (highest versus lowest, hazard ratios women 5.75 and men 3.43 for any OF; women 101.6 for HF). Calibration differences were noted, with both over- and underestimation in risk. Conclusions: Garvan FRC outperformed CRFs and BMD alone for fracture risk stratification, particularly for HF, but may require recalibration for accurate predictions in this population. [ABSTRACT FROM AUTHOR]

Summary: The risk of subsequent major osteoporotic and hip fracture following an initial fracture was increased in both sexes over 25 years, with modest time-dependent attenuation. This risk was highest in men, underscoring the importance of targeted treatment strategies particularly in this under-treated population. Introduction: The risk of subsequent fractures is increased following an index fracture, and declines over time. We aimed to determine whether this risk was sustained over 25 years and evolved similarly in men and women. Methods: Using population-based databases, we performed a matched cohort study in 16,876 men and 39,230 women ≥ 50 years who sustained an index fracture during 1989–2006. Rates of subsequent major osteoporotic fractures (MOF) and hip fractures until 2016 were compared to rates for matched controls (n = 160,983). Age- and sex-stratified cumulative incidences to 25 years were estimated in the presence of competing mortality. Hazard ratios (HRs) with 95% confidence intervals (CI) for subsequent fractures were estimated for each on the first 15 years of follow-up with a final category ≥ 15 years, adjusted for comorbidities. Results: Risk for MOF and hip fractures remained elevated up to 25 years in both sexes. The cumulative incidence of fractures was higher in cases vs controls in both sexes and across all age categories except in those > 90 years. Crude rate ratios for subsequent MOF were 2.5 (95% CI 2.3–2.7) in men and 1.6 (95% CI 1.6–1.7) in women and were higher in the younger age groups. Adjusted HRs (aHRs) for subsequent MOF were higher in men than in women in the first year (men aHR 2.6, 95% CI 2.1–3.3; women aHR 1.6, 95% CI 1.4–1.7). Conclusions: The risk of subsequent fractures following an initial fracture was increased over 25 years and the magnitude of risk was initially greater in men than in women. [ABSTRACT FROM AUTHOR]

Summary: Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. Introduction: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. Methods: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50–80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. Results: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of − 1.5(1.0) and − 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of − 1.9(0.9) and − 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ − 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. Conclusion: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65. [ABSTRACT FROM AUTHOR]

Summary: We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health. Introduction: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. Methods: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). Results: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 <.001, RMSEA =.03, TLI =.99, CFI =.99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p <.001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p <.001). Conclusions: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds. [ABSTRACT FROM AUTHOR]

Summary: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Introduction: Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Methods: Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. Results: The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08–1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47–1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. Conclusions: High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk. [ABSTRACT FROM AUTHOR]

Aims Undercarboxylated osteocalcin (ucOC) promotes increased insulin sensitivity and increased secretion. Since antiresorptive therapy (AT) decreases ucOC levels, AT could increase the risk of diabetes and this would have serious clinical ramifications. We sought to test this hypothesis by examining the association between new use of AT and newly-diagnosed diabetes. Methods Using a bone mineral density (BMD) registry for Manitoba, Canada, we identified 33 640 women aged ≥50 years without diabetes at their first BMD test for 1998-2013. We linked these women to a province-wide retail pharmacy database to identify new AT exposure each year for up to 5 years after a BMD test. Time-dependent analysis was used to test the independent association between new use of AT and newly diagnosed diabetes. Results This cohort had a mean age of 65 years, a mean body mass index of 26.8 kg/m2, and 12% were receiving glucocorticoid and 13% hormone replacement therapy at BMD test. In the first year after BMD test, 29% of women started AT (bisphosphonates, 92%). Over a mean 4.2 years of follow-up, 3.7% new AT users and 4.2% non-users had diabetes (adjusted hazard ratio 1.01, 95% confidence interval 0.87-1.16). Sensitivity analyses using AT dose-response gradients also found no significant associations with diabetes. Conclusions Despite the plausible biological mechanisms related to ucOC, new use of AT was not a risk factor for diabetes in this cohort. The clinical implications of these findings are reassuring, as AT is widely prescribed for treating osteoporosis in older women who are also at high risk of developing diabetes. [ABSTRACT FROM AUTHOR]

Summary: In an observational study population of 62,413 individuals (6,455 [10 %] with diabetes), diabetes was independently associated with major osteoporotic fractures (MOFs) but did not significantly modify the effect of FRAX risk factors or prior fracture site. However, the presence of diabetes exerted a much stronger effect on hip fracture risk in younger versus older individuals. Introduction: Diabetes mellitus increases fracture risk independent of risk factors that comprise the WHO FRAX tool. We explored whether diabetes modifies the effect of FRAX clinical risk factors on MOF and hip fracture risk. Methods: Using a registry of clinical dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified women and men aged 40 years and older undergoing baseline DXA in 1996-2011. Health services data were used to identify diabetes diagnosis, FRAX risk factors and incident fractures using previously validated algorithms. Prior fracture was stratified as clinical vertebral, hip, humerus, forearm, pelvis and 'other'. Cox proportional hazards models were used to test for statistical interactions of diabetes with FRAX clinical risk factors and prior fracture site. Results: During a mean follow-up of 6 years, there were 4,218 MOF and 1,108 hip fractures. Diabetes was a significant independent risk factor for MOF adjusted for FRAX risk factors including bone mineral density (BMD) (adjusted hazard ratio [aHR] 1.32 [95 % confidence interval (CI) 1.20-1.46]). No significant interactions of FRAX risk factors or prior fracture site with diabetes were identified in analyses of MOF. For predicting hip fractures, age significantly modified the effect of diabetes (aHR age <60, 4.67 [95 % CI 2.76-7.89], age 60-69, 2.68 [1.77-4.04], age 70-79, 1.57 [1.20-2.04], age >80, 1.42 [1. 10-1.99]; pinteraction <0.001). Conclusions: Diabetes is an independent risk factor for MOFs and does not significantly modify the effect of FRAX risk factors or prior fracture site. However, diabetes exerts a much stronger effect on hip fracture risk in younger than older individuals which needs to be considered in hip fracture prediction. [ABSTRACT FROM AUTHOR]

Summary: This study provides evidence that a number of frailty-related characteristics (older age, de novo admission to long-term care (LTC), comorbidities [Charlson Index, osteoporosis, osteoporosis risk factors, sarcopenia risk factors, and dementia]) have increased in the hip fracture population from 2001-2008. This will have significant impact on community resources, as the number of people discharged to the community is also increasing. Introduction: The aim of this study is to estimate secular changes in the prevalence of selected frailty-related characteristics among the hip fracture population in the Canadian province of Quebec (2001-2008) and the potential impact of these changes on healthcare services. Methods: The Quebec hospitalization database was used to identify nontraumatic hip fractures for the purposes of calculating age- and sex-specific rates. Also estimated were time trends for selected frailty-related characteristics and discharge destinations. Results: A significant decline in fracture rates was evident for all age groups except for those <65; sex differences were also observed. Almost all frailty-related characteristics increased over time, ranging from 2 to 14 % per year, which translates to an estimated increase from 16 to 112 %, over the study period. For those whose prior living arrangement was LTC, rates of hip fractures declined significantly (women OR = 0.93, 0.91-0.95; men OR = 0.97, 0.94-0.99). In-hospital mortality and discharge to inpatient rehabilitation decreased, while discharges back to community and to LTC increased. Conclusions: Although hip fracture rates decreased for older hip fracture patients, the absolute number and prevalence of specific frailty-related characteristics increased. Policy makers should review care models to ensure that adequate resources are provided to the community to offset the expected increase in demand arising from ongoing changes in patients' characteristics. [ABSTRACT FROM AUTHOR]

Summary: Although systemic glucocorticoids are commonly used, it is difficult to obtain accurate exposure history. In 50,000 patients, we confirmed that glucocorticoids were associated with reductions in bone mineral density (BMD) and increases in fracture and documented that recent and prolonged durations of exposure were particularly associated with adverse events-dose information did not improve risk prediction. Introduction: Systemic glucocorticoid use, defined as ever having taken supra-physiologic doses for 90-days or more, is a risk factor for low BMD and fractures. This definition does not distinguish recent (vs remote) exposure. Methods: Within a population-based clinical BMD registry in Manitoba, Canada, we identified all adults over age 40 years tested between 1998 and 2007 and then undertook a cohort study. We identified all oral glucocorticoid dispensations from 1995 to 2009 and stratified exposure by timing ('recent' if within 12 months vs 'remote') and duration (short [<90 days] vs prolonged [≥90 days]). Osteoporosis-related risk factors and treatments and major fractures were obtained using administrative health data. Results: A total of 12,818 of 52,070 (25 %) subjects had used glucocorticoids prior to BMD testing; the most common exposure was remote short ( n = 6453) vs recent prolonged ( n = 2896) vs recent short ( n = 2644) vs remote prolonged ( n = 825). Compared to 39,252 never-users, only recent prolonged glucocorticoid use was significantly associated with femoral neck T-score (ANCOVA-adjusted difference −0.13, 95 % CI −0.16 to −0.10, p < 0.001). There were 2,842 major (566 hip) fractures over median 5-year follow-up. Compared with never-users, only recent prolonged glucocorticoid use was significantly associated with BMD-independent increases in risk of incident major fracture (5.4 vs 7.7 %, adjusted HR 1.25, 95 % CI 1.07-1.45, p = 0.004) and hip fracture (1.1 vs 1.8 %, adjusted HR 1.61, 95 % CI 1.18-2.20, p = 0.003). Conclusions: Recent and prolonged glucocorticoid use (but neither remote nor recent short courses) was independently associated with reduced BMD and increased risk of fractures. These findings should permit clinicians to identify a high-risk group of patients that might benefit from osteoporosis prevention. [ABSTRACT FROM AUTHOR]